DRUG INTERACTIONS

REDUCED RATE OF ABSORPTION

-Area under curve is independent of absorption rate same total whether rate is rapid (IV) or slow (PO) Area under the curve is same
B Normal absorption C Reduced absorption

FRACTION & ABSORPTION RATE REDUCTION

-Drug 2 (Antacids) quantity & absorption rate of Drug 1 -Area under curve is reduced due to reduction of the fraction of the dose that is absorbed
B Normal absorption C Reduced rate and fraction absorbed

80 70 60

Concentration

Concentration
0 0 10 20 30 40 50 60

50 40 30 20 10 0 0 2 4 6

Time ( hr)

Time

10

12

14

16

REDUCED RATE OF ELIMINATION

-Concentration above normal b/c elimination is impaired -Drug 2 interferes w/ kidneys excretion of Drug 1
Abs. Normal Elim Reduced

ENZYME INDUCTION
-Drug 2 enhances levels of p450 action/loss of Drug 1 1. Barbituates action of Coumadin & Digitoxin 2. Phenytoin action of Cortisol, Digitoxin, & Theophylline

ENZYME INHIBITION
-Drug 2 inhibits p450 metabolism of Drug 1 1. Cimetidine (gastric acid inhibitor) metabolism of Diazepam, Quinidine, etc 2. EtOH metabolism of Diazepam, etc.
0 0 10 20 30 40 50 60

Concentration

Time

DRUG-DRUG INTERACTION
May have opposing or synergistic effect Antagonistic Effects: Cholinergic & Adrenergics Addictive Effects: Much greater effect w/ 2 drugs Commonly, pt take unknowingly several different products containing the same NSAID (OTC Ibuprofen & Rx) risk of Adverse Effects Ex. Chloropromazine (antipsychotic) & Amitryptyline (antidepressant) results in excessive anticholinergic effects: a. Dry mouth, associated dental complications, blurref vision, Hyperpyrexia in pt exposed to temp & humidity Thiazide Diuretics ( BP) TGs, Blood Sugar; avoid if diabetic

PROTEIN BINDING
-If a drug is normally bound to plasma proteins (Albumin) drug interaction w/ receptor & drug transfer out of the vascular compartment -Drug 2 competitively binds to protein Drug 2 = 1 drug 1. Drug 1 (Tolbutamine) binds to protein (Albumin) 2. Drug 2 (Sulfonamide) competes for receptor 3. Transient [Drug 1]

1.

2.

ADDITIVE & SYNERGISTIC INTERACTIONS

Additives have same 1 action (Tylenol, Advil) Dose remains same whether w/ or w/o additive Synergy effect goes beyond predicted effect based on individual potency take dose good & bad Ex. EtOH + Barbituates = too much sedation